title: Disruption of glycogen synthase kinase-3-beta activity leads to abnormalities in physiological measures in mice.
abstract: Dysregulation of glycogen synthase kinase-3-beta (GSK-3β) signaling pathways is thought to underlie the pathophysiology of mood disorders. In order to demonstrate that the loss of normal GSK-3β activity results in disturbances of physiological measures, we attempted to determine whether sleep-wake architecture, circadian rhythms of core body temperature and activity were altered in transgenic mice overexpressing GSK-3β activity specifically in the brain. Cortical electroencephalographic activity, body temperature (BT) and body locomotor activity (LMA) were continuously monitored using a biopotential telemetry probe. Normal circadian patterns were maintained for different measurements in both genotypes. No differences were found in total time spent asleep and waking over the 24-h recording session. However, transgenic animals overexpressing GSK-3β showed alteration in sleep continuity characterized by an increases in number of non rapid eye movement (NREM) sleep episodes (GSK-3β, 227.2 ± 1.7 vs. WT, 172.6 ± 1.4, p < 0.05) and decreases in mean episode duration (GSK-3β, 3.0 ± 0.1 vs. WT, 4.4 ± 0.2, p < 0.05). Additionally, transgenic animals exhibited marked enhancement of basal LMA and BT levels during the first part of the dark period, under both light-dark and free running dark-dark circadian cycles. Our findings indicate that transgenic mice overexpressing GSK-3β activity exhibit severe fragmentation of sleep-wake cycle during both the light and dark periods, without showing deviancy in total durations of vigilance states. The results strongly suggest that GSK-3β activity is elemental for the maintenance of circadian motor behavior levels required for proper regulation of BT and sleep-wake organization.
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, Dept of Neurosciences, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. aahnaou@prdbe.jnj.com
authors.forename: A
authors.initials: A
authors.lastname: Ahnaou
authors.forename: W H I M
authors.initials: WH
authors.lastname: Drinkenburg
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004569:Electroencephalography / Q000379:methods; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D017440:Photoperiod; D017286:Polysomnography / Q000379:methods; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D013686:Telemetry / Q000379:methods
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3